Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
Ann Nucl Med. 2022 Dec;36(12):1019-1030. doi: 10.1007/s12149-022-01790-0. Epub 2022 Sep 30.
Recent studies suggest that selective serotonin reuptake inhibitors (SSRIs) and exposure therapies have been used to reduced footshock-induced posttraumatic stress disorder (PTSD) symptoms. However, the therapeutic effect of the combination of SSRIs treatment with exposure therapy remains a matter of debate. This study aimed to evaluate these therapeutic effect through the behavioural and the neuroimaging changes by positron emission tomography (PET) in model rats.
Pavlovian fear conditioning paradigm to establish model rats, and serial PET imaging with 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) was performed during the control, fear-conditioning, and extinction-retrieval phases. The expression of c-Fos was used to identify neural activity.
We report that fear conditioning increased glucose metabolism in the right amygdala and left primary visual cortex but decreased glucose metabolism in the left primary somatosensory cortex. After extinction retrieval, there was increased [F]FDG uptake in the left striatum, left cochlear nucleus and right primary visual cortex but decreased uptake in the anterior cingulate cortex in the extinction group. Fluoxetine increased [F]FDG uptake in the left hippocampus and right primary visual cortex but decreased uptake in the bilateral primary somatosensory cortex, left primary/secondary motor cortex and cuneiform nucleus. The combined therapy increased [F]FDG uptake in the left hippocampus, left striatum, right insular cortex, left posterior parietal cortex, and right secondary visual cortex but reduced uptake in the cerebellar lobule. c-Fos expression in the hippocampal dentate gyrus and anterior cingulate cortex in the fluoxetine and combined groups was significantly higher than that in the extinction group, with no significant difference between the two groups.
Chronic fluoxetine enhanced the effects of extinction training in a rat model of PTSD. In vivo PET imaging may provide a promising approach for evaluation chronic fluoxetine treatment of PTSD.
最近的研究表明，选择性 5-羟色胺再摄取抑制剂（SSRIs）和暴露疗法已被用于减轻足底电击诱导的创伤后应激障碍（PTSD）症状。然而，SSRIs 联合暴露疗法的治疗效果仍存在争议。本研究旨在通过正电子发射断层扫描（PET）评估模型大鼠的行为和神经影像学变化来评估这种治疗效果。
采用条件性恐惧反应范式建立模型大鼠，在对照、恐惧条件、消退检索三个阶段进行连续的 2-脱氧-2-[F]氟-D-葡萄糖（[F]FDG）PET 成像。使用 c-Fos 表达来识别神经活动。
我们报告说，恐惧条件增加了右侧杏仁核和左侧初级视觉皮层的葡萄糖代谢，但减少了左侧初级体感皮层的葡萄糖代谢。在消退检索后，在消退组中，左侧纹状体、左侧耳蜗核和右侧初级视觉皮层的[F]FDG 摄取增加，而前扣带皮层的摄取减少。氟西汀增加了左侧海马体和右侧初级视觉皮层的[F]FDG 摄取，但减少了双侧初级体感皮层、左侧初级/次级运动皮层和楔前核的摄取。联合治疗增加了左侧海马体、左侧纹状体、右侧岛叶、左侧后顶叶皮层和右侧次级视觉皮层的[F]FDG 摄取，但减少了小脑小叶的摄取。氟西汀和联合治疗组海马齿状回和前扣带皮层的 c-Fos 表达明显高于消退组，两组之间无显著性差异。
慢性氟西汀增强了 PTSD 大鼠模型中消退训练的效果。体内 PET 成像可能为评估慢性氟西汀治疗 PTSD 提供一种有前途的方法。
